On the Disulfiram‐Like Effect of Coprine, the Pharmacologically Active Principle of Coprinus atramentarius

Abstract

Coprine or disulfiram was given to rats in various doses at various time intervals before the administration of 2 g/kg ethanol. The ratio acetaldehyde/ethanol in the alveolar air was measured by gas chromatography and was taken as an index of the aldehyde dehydrogenase (ALDH) activity. The activity of dopamine β‐hydroxylase (DBH) was estimated in the same animals by measuring the amount of 14C‐octopamine formed from 14C‐tyramine in the heart. Coprine and disulfiram both caused an increase in the acetylaldehyde/ethanol ratio, coprine being more potent than disulfiram. Disulfiram, but not coprine, reduced the net yield of 14C‐octopamine. In rats pretreated with either coprine or disulfiram, blood‐pressure and heart‐rate were recorded before and after intraperitoneal injections of 0.4 g/kg ethanol. In both cases ethanol caused a marked and rapid fall in blood‐pressure. However, this effect was accompanied by tachycardia only in animals treated with coprine. It is concluded that coprine like disulfiram inhibits ALDH, but only disulfiram causes an additional inhibition of DBH. This difference may account for differences in the cardiovascular response to ethanol

Mycetism: A Review of the Recent Literature

“…[79]. C. atramentarius contains coprine, a pro-toxin of 1-amino-cyclopropanol which inhibits acetaldehyde dehydrogenase; however, it does not inhibit dopamine-beta hydroxylase, as does disulfiram [79,80]. A disulfiram-like reaction ensues if ethanol is ingested within 30 min to 3 days after mushroom ingestion and can occur within several minutes of ingesting ethanol [79].…”

Aldehyde Dehydrogenase Inhibitors: a Comprehensive Review of the Pharmacology, Mechanism of Action, Substrate Specificity, and Clinical Application

“…The esterase activity of ALDH is also inhibited, albeit to a lesser extent compared with the dehydrogenase activity (Marchner and Tottmar, 1983). Unlike disulfiram (see below), it does not inhibit dopamine ␤-hydroxylase (Carlsson et al, 1978;Tottmar and Hellstrom, 1979). Despite its potency at inhibiting ALDH activity, mutagenic and gonadotoxic side effects prevented further pursuit of this compound as a candidate for drug development (Michelot, 1992).…”

Blood Pressure Response to Ethanol in Relation to Acetaldehyde Levels and Dopamine‐β‐hydroxylase Activity in Rats Pretreated with Disulfiram, Cyanamide and Coprine

“…Previous studies have shown that the inhibition of DBH and ALDH in disulfiram-treated rats is markedly different with respect to time-and doseresponse (Carlsson et al 1978;Deitrich & Erwin 1971). By using this difference, it was thought possible to gain some information about the relative importance of these two enzymes for the alcohol-sensitizing effects produced by disulfiram.…”

“…The DBHactivity in the heart in vivo was estimated from the rate of formation of I4C-octopamine from injected ''C-tyramine (Almgren et a/. 1965;Carlsson et al 1978). I4C-tyramine (14 pg/kg, 4 pCi/kg) was injected intravenously to anaesthetized rats (hexobarbital sodium, 150 mg/kg, intraperitoneally).…”